This project will study the natural killer (NK) cell defect in patients with chronic granulocytic leukemia (plus or minus blast crisis) and chronic lymphocytic leukemia (CLL) using a panel of combined in vitro morphological, phenotypical and functional criteria. Using these criteria, questions aimed at defining the precise differentiation level of NK cells will be asked. Similar criteria will be applied to the evaluation of natural killer cells in patients with acute lymphoblastic leukemia and a variety of non-Hodgkin's lymphomas. An additional goal is to continue to further characterize as well as to increase the NK susceptibility of fresh neoplastic leukemia/ lymphoma targets from these same patients using short-term culture and density gradient separation procedures. Amplification strategies, aimed at restoring the NK defect(s) in these patients, will consist of short-term activation with leukocyte interferon(s) [crude alpha and/or cloned, recombinant alpha], interleukin-2, and allogeneic stimulator cells. Additional amplification strategies will involve the long-term culturing of highly purified natural killer cells (plus or minus single cell cloning) in conditioned media containing interleukin-2 as well as in the presence of allogeneic and/or autologous feeder cells. Natural killer cells will be highly purified using flourescence-activated cell sorting (FACS) coupled with specific staining by the mouse monoclonal antibody HNK-1. Additional monoclonal antibodies such as B73.1, which also marks and defines a population of human NK cells will similarly be used to purify and characterize human NK cells in these patients. These experiments involving NK cells from patients with leukemia/lymphoma will always be compared to similarly prepared normal controls. The ultimate goal of this proposal is to demonstrate autologous natural killing using the above in vitro methodologies which augment NK cells and increase the susceptibility of fresh autologous leukemia/lymphoma targets. The in vitro demonstration of interferon-\and/or interleukin-augmented autologous natural killing is crucial to the eventual clinical use of interferon(s) and interleukin(s) as immunotherapeutic modalities for the treatment of leukemia/lymphoma patients with NK-susceptible tumor cells.